The interplay between undifferentiated and differentiated tissue allows the fine regulation of body homeostasis. Much is unknown about the molecular events underlying this process, but it is likely to involved adult stem cell activation. In addition to homeostasis, stem cells may be harnessed to induce the regeneration of tissue damaged by senescence, cancer, or injury. Such biomedical approaches require a basic molecular understanding of stem cells in their natural behavior. In complement to the current focus on biochemical signals, we will explore an important but largely mysterious set of cellular control parameters: ion flows. The main hypothesis that will be tested in this proposal is that stem cells are controlled in part by biophysical signals mediated by gap junctional communication and the activity of ion channels and pumps. Capitalizing on a powerful model system, the planarian, I propose to gain molecular, mechanistic insight into the novel and important role of endogenous physiological signals regulating the interactions between adult stem cells and differentiating tissue during physiological turnover.and regeneration.